rs7303577

Positions:

• chr12-64480322-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_013254.4(TBK1):​c.812+200A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,190 control chromosomes in the GnomAD database, including 1,967 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (1967 hom., cov: 32)
• Consequence: TBK1 NM_013254.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.222

Genes affected

TBK1 (HGNC:11584): (TANK binding kinase 1) The NF-kappa-B (NFKB) complex of proteins is inhibited by I-kappa-B (IKB) proteins, which inactivate NFKB by trapping it in the cytoplasm. Phosphorylation of serine residues on the IKB proteins by IKB kinases marks them for destruction via the ubiquitination pathway, thereby allowing activation and nuclear translocation of the NFKB complex. The protein encoded by this gene is similar to IKB kinases and can mediate NFKB activation in response to certain growth factors. The protein is also an important kinase for antiviral innate immunity response. [provided by RefSeq, Sep 2021]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 12-64480322-A-C is Benign according to our data. Variant chr12-64480322-A-C is described in ClinVar as [Benign]. Clinvar id is 1285973.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBK1	NM_013254.4	c.812+200A>C		intron_variant		ENST00000331710.10
TBK1	XM_005268809.2	c.812+200A>C		intron_variant
TBK1	XM_005268810.2	c.812+200A>C		intron_variant
TBK1	XR_007063071.1	n.911+200A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBK1	ENST00000331710.10	c.812+200A>C		intron_variant		1	NM_013254.4	P4

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22332 AN: 152072 Hom.: 1960 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0250

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.164

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.147 AC: 22370 AN: 152190 Hom.: 1967 Cov.: 32 AF XY: 0.146 AC XY: 10873 AN XY: 74394

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.0249

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.162

Alfa AF: 0.145 Hom.: 384

Bravo AF: 0.149

Asia WGS AF: 0.0970 AC: 336 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7303577; hg19: chr12-64874102;